Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir, a randomised non-inferiority trial

Abstract

BACKGROUND AIMS Direct-acting antiviral (DAA) therapy for HCV has high efficacy and limited toxicity. We hypothesised that the efficacy of glecaprevir-pibrentasvir for chronic HCV with a simplified treatment monitoring schedule would be non-inferior to a standard treatment monitoring schedule. METHODS In this open-label multicentre phase IIIb trial, treatment-naïve adults with chronic HCV without cirrhosis were randomly assigned (2:1) to receive glecaprevir-pibrentasvir 300 mg-120 mg daily for 8 weeks administered with a simplified or standard monitoring strategy. Clinic visits occurred at baseline and post-treatment week 12 in the simplified arm, and at baseline, week 4, week 8, and post-treatment week 12 in the standard arm. Study nurse phone contact occurred at week 4 and week 8 in both arms. Participants requiring adherence support were not eligible, including those reporting recent injecting drug use. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12), with a non-inferiority margin of 6%. RESULTS Overall, 380 participants (60% male, 47% genotype 1, 32% genotype 3) with chronic HCV were randomised and treated with glecaprevirpibrentasvir in the simplified (n = 253) and standard (n = 127) arms. In the intention-to-treat population, SVR12 was 92% (95% CI 89%-95%) in the simplified and 95% (95% CI 92%-99%) in the standard arm (difference between arms -3.2%; 95% CI -8.2% to 1.8%) and did not reach non-inferiority. In the perprotocol population, SVR12 was 97% (95% CI 96%-99%) in the simplified and 98% (95% CI 96%-100%) in the standard arm. No treatment-related serious adverse events were reported. CONCLUSIONS In patients with chronic HCV infection without cirrhosis, treatment with glecaprevir-pibrentasvir was safe and effective. In comparison to standard monitoring, a simplified monitoring schedule did not achieve non-inferiority. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT03117569. LAY SUMMARY Direct-acting antiviral (DAA) therapy for hepatitis C is highly effective and well tolerated. The SMART-C randomised trial evaluated an 8-week regimen of glecaprevir-pibrentasvir for hepatitis C treatment, using a simplified monitoring schedule that included no pathology tests or clinic visits during treatment. This simplified strategy produced a high cure rate (92%), but this was not equivalent to the standard monitoring schedule cure rate (95%).

Efficacy and Safety of Glecaprevir/Pibrentasvir for Chronic Hepatitis C Patients: A Systematic Review and Meta-analysis

“…The SVR12 rate in the ITT population was 92%, possibly because 14 patients were lost to follow up. 17 Consistent with our findings, SVR12 rates were not influenced by the presence or absence of cirrhosis in real world studies. 28,29 Currently, glecaprevir/pibrentasvir is not recommended for patients with decompensated cirrhosis (Child-Pugh B and Child-Pugh C) due to elevated drug exposures.…”

Glecaprevir/pibrentasvir for patients with chronic hepatitis C virus infection: Real‐world effectiveness and safety in Taiwan

“…[20][21][22][23][24][25][26][27]35,36 In addition, our data were also consistent with a recent SMART-C study, in which the on-treatment week 4 HCV virokinetics were not predictive of SVR 12 . 37 Because patients can achieve excellent SVR 12 rates without the need for on-treatment week 4 HCV RNA monitoring, applying GLE/PIB for HCV is economic saving and may overcome the huge barrier to community prescribing. 37 Although we did not have pre-treatment subgenotyping data for HCV GT 3 patients, one patient was confirmed to have HCV GT 3b infection at the time of relapse.…”

“…37 Because patients can achieve excellent SVR 12 rates without the need for on-treatment week 4 HCV RNA monitoring, applying GLE/PIB for HCV is economic saving and may overcome the huge barrier to community prescribing. 37 Although we did not have pre-treatment subgenotyping data for HCV GT 3 patients, one patient was confirmed to have HCV GT 3b infection at the time of relapse. This finding was line with two recent studies showing that the SVR 12 rates of GLE/PIB and SOF/VEL were suboptimal for HCV GT 3b due to the presence of high NS5A resistance-associated substitution (RAS) rates.…”

Are all cirrhotic patients equal?

“…High portal pressure is not a contraindication for antiviral therapy per se, but in a study using different sofosbuvir-based regimens viral clearance in patients with clinical significant portal hypertension took longer than 8 weeks. 19 Such patients should be evaluated by specialists to decide on an individual basis which drug combination is needed and how long treatment is required. glecaprevir/pibrentasvir is contraindicated in Child C cirrhosis and not recommended in Child B.…”